ABSTRACT
AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a diagnosis of exclusion that can pose a challenge to the pathologist despite thorough clinical workup. Although several immunohistochemical markers have been proposed for iCCA, none of them reached clinical practice. We here assessed the combined usage of two promising diagnostic approaches, albumin in situ hybridisation (Alb-ISH) and C reactive protein (CRP) immunohistochemistry, for distinguishing iCCA from other adenocarcinoma primaries. METHODS: We conducted Alb-ISH and CRP immunohistochemistry in a large European iCCA cohort (n=153) and compared the results with a spectrum of other glandular adenocarcinomas of different origin (n=885). In addition, we correlated expression patterns with clinicopathological information and mutation data. RESULTS: Alb-ISH was highly specific for iCCA (specificity 98.8%) with almost complete negativity in perihilar CCA and only rare positives among other adenocarcinomas (sensitivity 69.5%). CRP identified the vast majority of iCCA cases (sensitivity 84.1%) at a lower specificity of 86.4%. Strikingly, the combination of CRP and Alb-ISH boosted the diagnostic sensitivity to 88.0% while retaining a considerable specificity of 86.1%. Alb-ISH significantly correlated with CRP expression, specific tumour morphologies and small or large duct iCCA subtypes. Neither Alb-ISH nor CRP was associated with iCCA patient survival. 16 of 17 recurrent mutations in either IDH1, IDH2 and FGFR2 affected Alb-ISH positive cases, while the only KRAS mutation corresponded to an Alb-ISH negative case. CONCLUSIONS: In conclusion, we propose a sequential diagnostic approach for iCCA, integrating CRP immunohistochemistry and Alb-ISH. This may improve the accuracy of CCA classification and pave the way towards a molecular-guided CCA classification.
ABSTRACT
OBJECTIVES: This comparative study aimed to evaluate intraoral digital photography (IODP) as assessment-tool for DMFT and number of implants (IMPL) compared to clinical diagnosis (CLIN) in an elderly population with high restorative status. Secondary research questions were whether an additional evaluation of panoramic radiographs (PAN-X) or raters' clinical experience influence the agreement. METHODS: Fifty patients (70.98±7.60 years) were enrolled for standardized CLIN and IODP. The clinical reference examiner and ten blinded raters evaluated the photographs without and with a PAN-X regarding DMFT and IMPL. CLIN were used as reference standard and differences to IODP and IODP-PAN-X findings were analysed descriptively. To assess intra-rater agreement, pairwise Gwet's AC1s of the three diagnostic methods CLIN, IODP and IODP+PAN-X were calculated. RESULTS: Compared to a DMFT of 22.10±3.75 (CLIN), blinded raters evaluated a DMFT of 21.54±3.40 (IODP) and 22.12±3.45 (IODP+PAN-X). Mean values for "Decayed" were 0.18±0.52 (CLIN), 0.45±0.46 (IODP) and 0.48±0.47 (IODP-PAN-X), while 11.02±5.97 (CLIN), 10.66±5.78 (IODP) and 10.93±5.91 (IODP+PAN-X) were determined for "Missing" and 10.90±5.61 (CLIN), 10.43±4.85 (IODP) and 10.71±5.11 (IODP+PAN-X) for "Filled". IMPL were 0.78±2.04 (CLIN), 0.58±1.43 (IODP), 0.78±2.04 (IODP+PAN-X). Gwet's AC1 using the mode of the blinded raters' assessment of "Decayed", "Missing" and IMPL compared to CLIN ranged from 0.81 to 0.89 (IODP) and 0.87 to 1.00 (IODP+PAN-X), while for "Filled" and DMFT they were 0.29 and 0.36 (IODP) as well as 0.33 and 0.36 (IODP+PAN-X), respectively. Clinical experience did not influence the agreement. CONCLUSIONS: Assessment of "Decayed", "Missing" and IMPL by IODP showed almost perfect agreement, whereas of "Filled" and DMFT revealed fair to moderate agreement with clinical findings. Additional PAN-X-evaluation increased agreement compared to IODP-diagnostics alone. IODP for the assessment of DMFT and IMPL might be a suitable method in large-scale epidemiological studies, considering high agreement in total values and miscellaneous agreement at patient-level.
